Student or educator? Sign up with your school email and get 6 months of Pro free.
Cited by 579

The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.

Topaz-Denoise: general deep denoising models for cryoEM and cryoET

Open access
Bepler, Tristan, Kelley, Kotaro, Noble, Alex J., Berger, Bonnie·2020·Nature Communications

Published version of a preprint

Abstract

Cryo-electron microscopy (cryoEM) is becoming the preferred method for resolving protein structures. Low signal-to-noise ratio (SNR) in cryoEM images reduces the confidence and throughput of structure determination during several steps of data processing, resulting in impediments such as missing particle orientations. Denoising cryoEM images can not only improve downstream analysis but also accelerate the time-consuming data collection process by allowing lower electron dose micrographs to be used for analysis. Here, we present Topaz-Denoise, a deep learning method for reliably and rapidly increasing the SNR of cryoEM images and cryoET tomograms. By training on a dataset composed of thousands of micrographs collected across a wide range of imaging conditions, we are able to learn models capturing the complexity of the cryoEM image formation process. The general model we present is able to denoise new datasets without additional training. Denoising with this model improves micrograph interpretability and allows us to solve 3D single particle structures of clustered protocadherin, an elongated particle with previously elusive views. We then show that low dose collection, enabled by Topaz-Denoise, improves downstream analysis in addition to reducing data collection time. We also present a general 3D denoising model for cryoET. Topaz-Denoise and pre-trained general models are now included in Topaz. We expect that Topaz-Denoise will be of broad utility to the cryoEM community for improving micrograph and tomogram interpretability and accelerating analysis.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41467-020-18952-1

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 4 references

Research works printed but not linked: 44

  1. Baxter, W. T., Grassucci, R. A., Gao, H. & Frank, J. Determination of signal-to-noise ratios and spectral SNRs in cryo-EM low-dose imaging of molecules. J. Struct. Biol. 166, 126–132 (2009). · DOI
  2. Sindelar, C. V. & Grigorieff, N. An adaptation of the Wiener filter suitable for analyzing images of isolated single particles. J. Struct. Biol. 176, 60–74 (2011). · DOI
  3. Penczek, P. A. Chapter Two—Image Restoration in Cryo-Electron Microscopy. In Methods in Enzymology (ed. Jensen, G. J.) Vol. 482, 35–72 (Academic Press, 2010). · DOI
  4. Merk, A. et al. Breaking Cryo-EM resolution barriers to facilitate drug discovery. Cell 165, 1698–1707 (2016). · DOI · Paper page
  5. Herzik, M. A., Wu, M. & Lander, G. C. High-resolution structure determination of sub-100 kDa complexes using conventional cryo-EM. Nat. Commun. 10, 1–9 (2019). · DOI
  6. Milanfar, P. A tour of modern image filtering: new insights and methods, both practical and theoretical. IEEE Signal Process. Mag. 30, 106–128 (2013). · DOI · Paper page
  7. Xie, J., Xu, L. & Chen, E. Image Denoising and Inpainting with Deep Neural Networks. In Advances in Neural Information Processing Systems 25 (eds Pereira, F., Burges, C. J. C., Bottou, L. & Weinberger, K. Q.) 341–349 (Curran Associates, Inc., 2012).
  8. Jain, V. & Seung, S. Natural Image Denoising with Convolutional Networks. In Advances in Neural Information Processing Systems 21 (eds Koller, D., Schuurmans, D., Bengio, Y. & Bottou, L.) 769–776 (Curran Associates, Inc., 2009).
  9. Lehtinen, J. et al. Noise2Noise: Learning Image Restoration without Clean Data. In Proc. 35th International Conference on Machine Learning (eds Dy, J. & Krause, A.) 2965–2974 (PMLR, 2018).
  10. Zhussip, M., Soltanayev, S. & Chun, S. Y. Extending Stein’s unbiased risk estimator to train deep denoisers with correlated pairs of noisy images. In Advances in Neural Information Processing Systems 32 (eds Wallach, H., Larochelle, H., Beygelzimer, A., Alche-Buc, F., Fox, E., & Garnett, R.), 1465–1475 (Curran Associates, Inc., 2019).
  11. Batson, J. & Royer, L. Noise2Self: blind denoising by self-supervision. In Proc. 36th International Conference on Machine Learning (eds Chaudhuri, K. & Salakhutdinov, R.) 524–533 (PMLR, 2019).
  12. Krull, A., Buchholz, T.-O. & Jug, F. Noise2Void—learning denoising from single noisy images. In Proc. IEEE/CVF Conference on Computer Vision and Pattern Recognition (CVPR) (2019). · DOI · Paper page
  13. Buchholz, T. O. et al. Content-aware image restoration for electron microscopy. Methods Cell Biol. 152, 277-289 https://doi.org/10.1016/bs.mcb.2019.05.001 (2019). · DOI
  14. Buchholz, T.-O. et al. Chapter 13—Content-aware image restoration for electron microscopy. In Methods in Cell Biology (eds Müller-Reichert, T. & Pigino, G.), Vol. 152, 277–289 (Academic Press, 2019). · DOI
  15. Tegunov, D. & Cramer, P. Real-time cryo-electron microscopy data preprocessing with Warp. Nat. Methods 16, 1146–1152 (2019). · DOI · Paper page
  16. Bepler, T. et al. Positive-unlabeled convolutional neural networks for particle picking in cryo-electron micrographs. Nat. Methods 16, 1153–1160 https://doi.org/10.1038/s41592-019-0575-8 (2019). · DOI · Paper page
  17. Morin, A. et al. Collaboration gets the most out of software. eLife 2, e01456 (2013). · DOI · Paper page
  18. Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290–296 (2017). · DOI · Paper page
  19. Lander, G. C. et al. Appion: an integrated, database-driven pipeline to facilitate EM image processing. J. Struct. Biol. 166, 95–102 (2009). · DOI · Paper page
  20. de la Rosa-Trevín, J. M. et al. Scipion: a software framework toward integration, reproducibility and validation in 3D electron microscopy. J. Struct. Biol. 195, 93–99 (2016). · DOI · Paper page
  21. Mao, Y. et al. Molecular architecture of the uncleaved HIV-1 envelope glycoprotein trimer. Proc. Natl Acad. Sci. USA 110, 12438–12443 (2013). · DOI
  22. Haider, S. A. et al. Fluorescence microscopy image noise reduction using a stochastically-connected random field model. Sci. Rep. 6, 20640 (2016). · DOI
  23. Liao, M., Cao, E., Julius, D. & Cheng, Y. Structure of the TRPV1 ion channel determined by electron cryo-microscopy. Nature 504, 107–112 (2013). · DOI · Paper page
  24. Stagg, S. M., Noble, A. J., Spilman, M. & Chapman, M. S. ResLog plots as an empirical metric of the quality of cryo-EM reconstructions. J. Struct. Biol. 185, 418–426 (2014). · DOI
  25. Frank, J. & Al-Ali, L. Signal-to-noise ratio of electron micrographs obtained by cross correlation. Nature 256, 376–379 (1975). · DOI
  26. Chen, M. et al. Convolutional neural networks for automated annotation of cellular cryo-electron tomograms. Nat Methods 14, 983–985 https://doi.org/10.1038/nmeth.4405 (2017). · DOI · Paper page
  27. Belthangady, C. & Royer, L. A. Applications, promises, and pitfalls of deep learning for fluorescence image reconstruction. Nat. Methods 16, 1215–1225 (2019). · DOI · Paper page
  28. Frank, J. Three-Dimensional Electron Microscopy of Macromolecular Assemblies. Academic Press (1996). · DOI
  29. Henderson, R. Avoiding the pitfalls of single particle cryo-electron microscopy: Einstein from noise. Proc. Natl Acad. Sci. USA 110, 18037–18041 (2013). · DOI
  30. Iudin, A., Korir, P. K., Salavert-Torres, J., Kleywegt, G. J. & Patwardhan, A. EMPIAR: a public archive for raw electron microscopy image data. Nat. Methods 13, 387–388 (2016). · DOI · Paper page
  31. Zheng, S. Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331–332 (2017). · DOI · Paper page
  32. Kremer, J. R., Mastronarde, D. N. & McIntosh, J. R. Computer visualization of three-dimensional image data using IMOD. J. Struct. Biol. 116, 71–76 (1996). · DOI
  33. Rohou, A. & Grigorieff, N. CTFFIND4: Fast and accurate defocus estimation from electron micrographs. J. Struct. Biol. 192, 216–221 (2015). · DOI · Paper page
  34. Tan, Y. Z. et al. Addressing preferred specimen orientation in single-particle cryo-EM through tilting. Nat. Methods 14, 793–796 (2017). · DOI · Paper page
  35. Pettersen, E. F. et al. UCSF Chimera–a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004). · DOI · Paper page
  36. Schaffer, M. et al. Optimized cryo-focused ion beam sample preparation aimed at in situ structural studies of membrane proteins. J. Struct. Biol. 197, 73–82 (2017). · DOI · Paper page
  37. Mastronarde, D. N. Automated electron microscope tomography using robust prediction of specimen movements. J. Struct. Biol. 152, 36–51 (2005). · DOI
  38. Suloway, C. et al. Fully automated, sequential tilt-series acquisition with Leginon. J. Struct. Biol. 167, 11–18 (2009). · DOI
  39. Noble, A. J. & Stagg, S. M. Automated batch fiducial-less tilt-series alignment in Appion using Protomo. J. Struct. Biol. 192, 270–278 (2015). · DOI
  40. Winkler, H. & Taylor, K. A. Accurate marker-free alignment with simultaneous geometry determination and reconstruction of tilt series in electron tomography. Ultramicroscopy 106, 240–254 (2006). · DOI
  41. Agulleiro, J. I. & Fernandez, J. J. Fast tomographic reconstruction on multicore computers. Bioinformatics 27, 582–583 (2011). · DOI · Paper page
  42. Agulleiro, J.-I. & Fernandez, J.-J. Tomo3D 2.0—exploitation of Advanced Vector eXtensions (AVX) for 3D reconstruction. J. Struct. Biol. 189, 147–152 (2015). · DOI
  43. Xu, H. et al. Structural basis of Nav1.7 inhibition by a gating-modifier spider toxin. Cell 176, 702–715.e14 (2019). · DOI
  44. Campbell, M. G., Veesler, D., Cheng, A., Potter, C. S. & Carragher, B. 2.8 Å resolution reconstruction of the Thermoplasma acidophilum 20S proteasome using cryo-electron microscopy. eLife 4, e06380 (2015). · DOI

Cited by

Metadata

Authors
Bepler, T., Kelley, K., Noble, A. J., & Berger, B.
Venue
Nature Communications
Published
2020-10-15
Volume
11
Issue
1
Pages
5208-5208
ISSN
2041-1723 (ISSN-L)
OpenAlex
W3093295276
Cited by
579
References
4
FWCI
25.50
Type
journal article
Language
en
Open access
gold
Licence
Funders
U.S. Department of Health & Human Services | NIH | Office of Extramural Research, National Institutes of Health (GM081871)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.